The Role of Trait Impulsivity and Novelty-Seeking as Predisposing Factors to the Acquisition and Reinstatement of MDMA Self-Administration

Abstract:

It has been suggested that the response to novelty and impulsivity predict the latency to acquisition and maintenance of drug self-administration, respectively. The aim of this thesis was to examine the relationship between these two traits and (1) the latency to acquisition and (2) maintenance (drug seeking) of 3,4-methylenedioxymethamphetamine (MDMA) self–administration. Impulsivity, measured as premature responding on the 5-choice serial reaction time task (5-CSRTT), and novelty seeking, measured as the locomotor response in a novel environment, were measured prior to self-administration. Due to characteristics of the rat strain and test equipment the 5-CSRTT was configurated in the first part of this study and modified from the standard version. Following training in this task animals were implanted with a siliastic catheter and were subsequently screened for their response to a novel environment prior to MDMA self-administration. Latency to acquisition was determined as the number of test sessions required to self-administer an initial criterion of 90 infusions of 1.0 mg/kg/infusion as well as an additional 150 infusions of 0.5 mg/kg/infusion MDMA. For some rats, the ability of MDMA (0, 5.0 or 10.0 mg/kg, IP) to produce drug seeking was subsequently measured and for others, impulsivity was again measured following self-administration. Novelty seeking predicted cocaine self-administration but was not significantly correlated with either the acquisition or drug-seeking measures of MDMA self-administration. Impulsivity was not significantly correlated with the latency to acquire self-administration of MDMA but was significantly and positively correlated with the magnitude of MDMA produced drug-seeking. Furthermore, MDMA self-administration produced a number of notable, but transient, deficits in the 5-CSRTT; there was an increase in omission rate and a delayed increase in premature responses in particular. These findings suggest that impulsivity, but not sensation seeking, might be a risk factor for the development of compulsive drug-seeking following withdrawal from MDMA self-administration. A surprising finding from this study was a high acquisition rate amongst rats that acquired the 5-CSRTT prior to self-administration. This difference was examined in a separate set of experiments. This effect could not be explained by an effect of handling, food restriction, or exposure to sweetened condensed milk and might possibly be due to differences in instrumental learning.